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To evaluate the ability of the neuroretinal rim (NRR) rules determined using spectral domain optical coherence tomography (SDOCT) in diagnosing glaucoma and to study the effect of optic disc size and disease severity on the diagnostic ability of these rules.In a cross-sectional study, 125 eyes of 96 glaucoma patients and 96 eyes of 72 control subjects underwent optic nerve head (ONH) imaging with SDOCT. Inferior (I), superior (S), nasal (N) and temporal (T) NRR areas were automatically determined by the sdoct software. Diagnostic abilities of ISNT (I > S > N > T), IT (I > T) and ST (S > T) rules in glaucoma were evaluated using sensitivity, specificity and likelihood ratios (LR). Effect of optic disc size and disease severity [based on mean deviation (MD) on visual fields] on the diagnostic ability of the NRR rules was evaluated using regression models.Sensitivities of ISNT, IT and ST rules were 80.8%, 60.0% and 29.6%, respectively, and the specificities were 32.3%, 84.4% and 93.8%, respectively. Positive LRs of ISNT, IT and ST rules were 1.19, 3.84 and 4.74, respectively, and negative LRs were 0.60, 0.47 and 0.75, respectively. Sensitivities of ISNT (coefficient: −1.06, p = 0.02) and IT (−0.71, 0.05) rules decreased with increasing disc size. Positive LR of IT rule increased significantly (−0.01, 0.04) with decreasing MD, and negative LR of IT rule decreased (got better) significantly (0.26, 0.05) with decreasing disc size.Neuroretinal rim rules, as determined by SDOCT, do not allow robust differentiation of glaucomatous from non-glaucomatous discs.